| First Author | Cho KK | Year | 2015 |
| Journal | Neuron | Volume | 85 |
| Issue | 6 | Pages | 1332-43 |
| PubMed ID | 25754826 | Mgi Jnum | J:221122 |
| Mgi Id | MGI:5638270 | Doi | 10.1016/j.neuron.2015.02.019 |
| Citation | Cho KK, et al. (2015) Gamma rhythms link prefrontal interneuron dysfunction with cognitive inflexibility in Dlx5/6(+/-) mice. Neuron 85(6):1332-43 |
| abstractText | Abnormalities in GABAergic interneurons, particularly fast-spiking interneurons (FSINs) that generate gamma (gamma; approximately 30-120 Hz) oscillations, are hypothesized to disrupt prefrontal cortex (PFC)-dependent cognition in schizophrenia. Although gamma rhythms are abnormal in schizophrenia, it remains unclear whether they directly influence cognition. Mechanisms underlying schizophrenia's typical post-adolescent onset also remain elusive. We addressed these issues using mice heterozygous for Dlx5/6, which regulate GABAergic interneuron development. In Dlx5/6(+/-) mice, FSINs become abnormal following adolescence, coinciding with the onset of cognitive inflexibility and deficient task-evoked gamma oscillations. Inhibiting PFC interneurons in control mice reproduced these deficits, whereas stimulating them at gamma-frequencies restored cognitive flexibility in adult Dlx5/6(+/-) mice. These pro-cognitive effects were frequency specific and persistent. These findings elucidate a mechanism whereby abnormal FSIN development may contribute to the post-adolescent onset of schizophrenia endophenotypes. Furthermore, they demonstrate a causal, potentially therapeutic, role for PFC interneuron-driven gamma oscillations in cognitive domains at the core of schizophrenia. |
